When E. coli cells are treated with sublethal levels of alkylating agents, they become more resistant to the mutagenic and lethal effects of subsequent high level treatments with alkylating agents. This increased resistance has been called the adaptive response and is the result of the induction of increased capacity to repair alkylation lesions in DNA. We have initiated a genetic study designed to learn what genes are induced by alkylation treatments, how they are regulated and what the functions of their products are. To date we have identified five genes or operons that are specifically induced by alkylation treatments by constructing fusions of the lac operon to promoters of genes induced by alkylation treatments. One of these alkylation inducible (aid) genes, or operons, (aidA) codes for the alkA gene product which is a glycosylase that removes methylated bases from DNA. aidD appears to be a fusion to the data operon, which codes for two gene products, at least one of which is a regulatory protein controlling the adaptive response. The other three loci represent new genes involved in this process. Our studies show that treatments with levels of alkylating agents that elicit the adaptive response are suboptimal, and induce only a subset of the alkylation inducible genes. At optimal concentrations of alkylating agents, addtional genes are induced. In addition, only four of the five loci are regulated by the ada gene. The fifth locus, aidC, is not only ada independent but is induced only by some methylating agents and not others. Thus the induction of genes by alkylation treatments is more complex than was originally revealed by studies of the adaptive response. We are now using these strains to learn how these aid genes are regulated and how their products function at the molecular level.